The present invention relates to serum or plasma separating compositions for use in centrifuging blood utilizing a difference in specific gravity between blood components, and to blood testing containers having the composition accommodated therein.
Blood testing containers for collecting blood therein are already known which have accommodated in the bottom thereof a serum or plasma separating thixotropic composition such as a mixture of silicone and silica (Unexamined Japanese Patent Publication No. 83654/1976). When blood is collected in the container, allowed to stand for a suitable period of time and thereafter centrifuged, the serum or plasma separating composition, which is in the form of a gel, is fluidized by the centrifugal force. In specific gravity, the gel of the composition is intermediate between the serum or plasma and the clot or cellular (corpuscle) component of the blood, so that the composition gradually rises from the bottom of the container through the collected blood and becomes positioned between a layer of serum or plasma and a layer of blood clot or cells, separating the serum or plasma from the clot or cellular component. The serum or plasma thus separated from the clot or cellular component can be readily withdrawn from the container and subjected to various tests, or can be preserved without being transferred to another container.
The compounds already known for use as the main component of such serum or plasma separating thixotropic compositions include, in addition to the above-mentioned silicone, .alpha.-olefin-maleic acid diester copolymer (Unexamined Japanese Patent Publications No. 66956/1981 and No. !68159/1990), polyester polymer (Unexamined Japanese Patent Publication No. 233368/1986), acrylic polymer (Unexamined Japanese Patent Publication No. 42283/1978), chlorinated polybutene (Unexamined Japanese Patent Publication No. 9718/1982), cyclopentadiene resin (Unexamined Japanese Patent Publication No. 295163/1989) and modified cyclopentadiene resin prepared by introducing a hydroxyl, ester, ether, epoxy or like group into cyclopentadiene resin (Unexamined Japanese Patent Publication No. 95257/1990). The materials to be admixed with such a main component as required include, for example, inorganic fillers such as silica, which serve as specific gravity adjusting agents and also as gelling agents for giving thixotropy, substances having a polar group at opposite ends of the molecule, such as propylene glycol and ethylenediamine (such fillers and substances being disclosed in Unexamined Japanese Patent Publication No. 295163/1989), and organic gelling agents such as condensation products of sorbitol and an aromatic aldehyde (Unexamined Japanese Patent Publication No. 168159/1990).
However, silicone forms a phase as distinctly separated from the inorganic filler, undergoes a curing reaction when sterilized by gamma-ray irradiation and is therefore almost out of use presently. .alpha.-Olefinmaleic acid diester copolymer, polyester polymer, acrylic polymer, modified cyclopentadiene resin and the like which have a polar group are relatively less likely to affect the determination of substances in the blood under clinical examination, but frequently exert an influence on the measurement of concentration of drugs in the blood (for example, the measurement of concentration of antiepileptics, such as phenobarbital, carbamazepine and phenytoin, in the blood).
On the other hand, the use of chlorinated polybutene entails the problem that when it is to be disposed of by incineration after use, the composition releases hydrochloric acid to cause damage to the incinerator.
Cyclopentadiene resin is superior in that it is free of these drawbacks, but the viscosity of the resin is dependent largely on temperature. Accordingly, it is likely that the serum or plasma separating composition consisting primarily of cyclopentadiene resin will exhibit poor fluidity and fail to function as such composition, for example, when treated for separation in a centrifuge set to a temperature of 4.degree. C. Stated more specifically, the composition consisting primarily of cyclopentadiene resin encounters no problem insofar as it is used approximately at room temperature, i.e., at 20.degree. C. to 25.degree. C., for centrifuging, whereas the composition with the main component of cyclopentadiene resin will not always form a satisfactory separating layer in the case where it is subjected to a centrifugal separation procedure at a temperature of 4.degree. C. using a centrifuge equipped with a refrigerator, as practiced recently to obviate the influence of heat released from the motor of the centrifuge.
To overcome the problem of separation failure, we previously conducted investigations on two-component compositions comprising cyclopentadiene resin and a gelling agent, and found that the composition was unable to exhibit sufficient fluidity when centrifuged at the set temperature of 4.degree. C. (Japanese Patent Application No. 335034/1990)
An object of the present invention is to provide a serum or plasma separating thixotropic composition which comprises a cyclopentadiene resin, a viscosity adjusting agent and an organic gelling agent and which is capable of giving a satisfactory separating layer even when subjected to a centrifugal separation procedure at the set temperature of 4.degree. C., and to provide a blood testing container having the composition accommodated therein.
The methods of sterilizing serum or plasma separating compositions include one wherein the composition is irradiated with gamma rays at a required dose.
The serum or plasma separating composition comprising a cyclopentadiene resin, a viscosity adjusting agent and an organic gelling agent and fulfilling the above object forms a satisfactory separating layer even when subjected to a centrifugal separation procedure at the set temperature of 4.degree. C., exerts no influence on the determination of concentration of drugs in blood and is superior to the conventional serum or plasma separating compositions.
Nevertheless, the composition fulfilling the foregoing object is likely to markedly bubble up when sterilized by gamma-ray irradiation because the composition is decomposed by-the irradiation and gasifies. Even when bubbling up and partly decomposed, the composition will not become impaired in its contemplated serum or plasma separating function although this depends on the degree of decomposition, whereas with the lapse of time, the viscosity adjusting agent becomes liable to form a phase separating from the composition. The decomposition due to the gamma-ray irradiation is therefore undesirable.
Another object of the present invention is to provide a serum or plasma separating composition capable of giving a satisfactory separating layer even when subjected to a centrifugal separation procedure at the set temperature of 4.degree. C., producing no influence on the determination of concentration of drugs in blood and having good stability without the likelihood of decomposing and bubbling up even if sterilized by gamma-ray irradiation, and to provide a blood testing container having the composition accommodated therein.